Detailed tandem repeat allele profiling in 1,027 long-read genomes reveals genome-wide patterns of pathogenicity.

ABSTRACT: Tandem repeats are a highly polymorphic class of genomic variation that play causal roles in rare diseases but are notoriously difficult to sequence using short-read techniques^1,2. Most previous studies profiling tandem repeats genome-wide have reduced the description of each locus to the singular value of the length of the entire repetitive locus^3,4. Here we introduce a comprehensive database of 3.6 billion tandem repeat allele sequences from over one thousand individuals using HiFi long-read sequencing. We show that the previously identified pathogenic loci are among the most variable tandem repeat loci in the genome, when incorporating nucleotide resolution sequence content to measure the longest pure motif segment. More broadly, we introduce a novel measure, 'tand

SUBMITTER: Danzi MC 

PROVIDER: S-EPMC11760257 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature